Identification of prognostic markers in diffuse midline gliomas H3K27M‐mutant

Pediatric diffuse midline gliomas are devastating diseases. Among them, diffuse midline gliomas H3K27M‐mutant are associated with worse prognosis. However, recent studies have highlighted significant differences in clinical behavior and biological alterations within this specific subgroup. In this context, simple markers are needed to refine the prognosis of diffuse midline gliomas H3K27M‐mutant and guide the clinical management of patients. The aims of this study were (i) to describe the molecular, immunohistochemical and, especially, chromosomal features of a cohort of diffuse midline gliomas and (ii) to focus on H3K27M‐mutant tumors to identify new prognostic markers. Patients were retrospectively selected from 2001 to 2017. Tumor samples were analyzed by immunohistochemistry (including H3K27me3, EGFR, c‐MET and p53), next‐generation sequencing and comparative genomic hybridization array. Forty‐nine patients were included in the study. The median age at diagnosis was 9 years, and the median overall survival (OS) was 9.4 months. H3F3A or HIST1H3B mutations were identified in 80% of the samples. Within the H3K27M‐mutant tumors, PDGFRA amplification, loss of 17p and a complex chromosomal profile were significantly associated with worse survival. Three prognostic markers were identified in diffuse midline gliomas H3K27M‐mutant: PDGFRA amplification, loss of 17p and a complex chromosomal profile. These markers are easy to detect in daily practice and should be considered to refine the prognosis of this entity.     

What are the visuo-motor tendencies of omnidirectional scene free-viewing in virtual reality?

Central and peripheral vision during visual tasks have been extensively studied on two-dimensional screens, highlighting their perceptual and functional disparities. This study has two objectives: replicating on-screen gaze-contingent experiments removing central or peripheral field of view in virtual reality, and identifying visuo-motor biases specific to the exploration of 360 scenes with a wide field of view. Our results are useful for vision modelling, with applications in gaze position prediction (e.g., content compression and streaming). We ask how previous on-screen findings translate to conditions where observers can use their head to explore stimuli. We implemented a gaze-contingent paradigm to simulate loss of vision in virtual reality, participants could freely view omnidirectional natural scenes. This protocol allows the simulation of vision loss with an extended field of view (>80°) and studying the head''s contributions to visual attention. The time-course of visuo-motor variables in our pure free-viewing task reveals long fixations and short saccades during first seconds of exploration, contrary to literature in visual tasks guided by instructions. We show that the effect of vision loss is reflected primarily on eye movements, in a manner consistent with two-dimensional screens literature. We hypothesize that head movements mainly serve to explore the scenes during free-viewing, the presence of masks did not significantly impact head scanning behaviours. We present new fixational and saccadic visuo-motor tendencies in a 360° context that we hope will help in the creation of gaze prediction models dedicated to virtual reality.     

Be Healthy in Pregnancy (BHIP): A Randomized Controlled Trial of Nutrition and Exercise Intervention from Early Pregnancy to Achieve Recommended Gestational Weight Gain

A randomized two-arm prospective superiority trial tested the efficacy of a novel structured and monitored nutrition (bi-weekly counselling for individualized energy and high dairy protein diet) and exercise program (walking goal of 10,000 steps/day) (intervention) compared to usual care (control) in pregnant women to achieve gestational weight gain (GWG) within current recommendations. Women recruited in communities in southern Ontario, Canada were randomized at 12–17 weeks gestation with stratification by site and pre-pregnancy BMI to intervention (n = 119) or control (n = 122). The primary outcome was the proportion of women who achieved GWG within the Institute of Medicine recommendations. Although the intervention compared to control group was more likely to achieve GWG within recommendations (OR = 1.51; 95% CI (0.81, 2.80)) and total GWG was lower by 1.45 kg (95% CI: (−11.9, 8.88)) neither reached statistical significance. The intervention group achieved significantly higher protein intake at 26–28 week (mean difference (MD); 15.0 g/day; 95% CI (8.1, 21.9)) and 36–38 week gestation (MD = 15.2 g/day; 95% CI (9.4, 21.1)) and higher healthy diet scores (22.5 ± 6.9 vs. 18.7 ± 8.5, p < 0.005) but step counts were similar averaging 6335 steps/day. Pregnancy and infant birth outcomes were similar between groups. While the structured and monitored nutrition with counselling improved diet quality and protein intake and may have benefited GWG, the exercise goal of 10,000 steps/day was unachievable. The results can inform future recommendations for diet and physical activity in pregnancy.     

Colorimetric capnography to ensure correct nasogastric tube position

Purpose

We evaluate a procedure, combining colorimetric capnography with epigastric auscultation, to ensure nasogastric (NG) feeding tube correct position without any radiograph.

Methods

We first evaluated the accuracy of colorimetric capnography in detecting tracheal positioning in a control group of 100 mechanically ventilated patients. The procedure was thereafter evaluated in a study group including patients requiring an NG tube. The NG tube was first inserted 30 cm and connected to a colorimetric capnograph (first step). If the capnograph did not detect carbon dioxide, insertion was completed to a total distance of 50 cm. An epigastric auscultation after air insufflation and a second capnography (second step) were performed. A radiograph evaluated correct tube position.

Results

In the control group, colorimetric capnograph sensitivity to detect tracheal placement was 100%. In the study group, negative predictive value of first-step capnography to rule out tracheobronchial insertion was 100%. The association of a first-step negative capnography with a positive epigastric auscultation correctly identified all but one gastric insertions, yielding a sensitivity of 98.5% (95% confidence interval, 95.7-100). The positive predictive value of this association to detect gastric placement was 100%.

Conclusion

Colorimetric capnography combined with epigastric auscultation is safe and accurate in ensuring correct gastric tube insertion.     

What about physical contacts between epidermal keratinocytes and sensory neurons?

Recent studies have demonstrated that keratinocytes closely participate in sensory transduction, and therefore, intra‐epidermal free nerve endings are not exclusive transducers of pain. This discovery implies the existence of close afferent communication from keratinocytes to sensory neurons. Although reciprocal interactions between keratinocytes and intra‐epidermal free nerve endings via soluble mediators are well established, little attention has been paid to physical contacts between keratinocytes and intra‐epidermal free nerve endings. This review proposes to consider the ultrastructural and functional knowledge of these contacts, in both human skin biopsies and keratinocyte‐sensory neuron cocultures to speculate on the possible existence of synaptic contacts.     

A meta-analysis of the efficacy of venlafaxine extended release 75–225 mg/day for the treatment of major depressive disorder

Objective: To evaluate the short-term efficacy of venlafaxine extended release (ER) 75–225?mg/day compared with placebo for treating major depressive disorder (MDD) and to examine associations between baseline characteristics and efficacy outcomes in MDD patients treated with venlafaxine ER 75–225?mg/day.

Research design and methods: This meta-analysis included published and unpublished short-term, double-blind, placebo-controlled, Wyeth/Pfizer sponsored studies of venlafaxine ER at doses up to 225?mg/day in adults with MDD.

Clinical trial registration: All trials were conducted before trial registration became mandatory.

Main outcome measures: Change from baseline in the 17-item Hamilton Rating Scale for Depression (HAM-D₁₇) total score was analyzed over time using a mixed-effects model for repeated measures with terms for study, treatment group, visit, interaction between treatment group and visit, and baseline score as a covariate. Associations between baseline demographic and clinical characteristics and the probability of HAM-D₁₇ response and remission at week 8 were evaluated using logistic regression models, with terms for study, treatment group, and baseline characteristics in the models. Safety and tolerability was assessed based on adverse events (AEs) and discontinuations due to AEs.

Results: The full analysis set included 1087 patients from five studies that fulfilled selection criteria. Statistically significant separation between venlafaxine ER and placebo groups for HAM-D₁₇ total score was seen at week 2 and all subsequent assessments (p-values <.0001). There was no significant interaction between treatment and baseline HAM-D₁₇ total score. Probability of HAM-D₁₇ remission at week 8 decreased with increasing baseline HAM-D₁₇ total score (p?=?.0012; OR: 0.94); however, baseline HAM-D₁₇ total score did not predict response. Discontinuations due to AEs were reported for 9.4% of venlafaxine-ER-treated patients compared with 3.6% of placebo-treated patients.

Key limitations: Five studies met the criteria for inclusion. Several differences in design between included studies limited the analysis: one study did not include a week 3 assessment (the week 3 time point was therefore dropped from the analysis), one study had two venlafaxine ER dose arms, which were combined into one group for the meta-analysis, and mixed- and flexible-dose studies were pooled.

Conclusions: Venlafaxine ER 75–225?mg/day effectively reduced symptoms of depression in patients with MDD overall and in patients with either lower (≤23) or higher (>23) HAM-D₁₇ total score at baseline.     

PiggyMac,a domesticated piggyBac transposase involved in programmed genome rearrangements in the ciliate Paramecium tetraurelia

Programmed genome rearrangements drive functional gene assembly in ciliates during the development of the somatic macronucleus. The elimination of germline sequences is directed by noncoding RNAs and is initiated by DNA double-strand breaks, but the enzymes responsible for DNA cleavage have not been identified. We show here that PiggyMac (Pgm), a domesticated piggyBac transposase, is required for these rearrangements in Paramecium tetraurelia. A GFP-Pgm fusion localizes in developing macronuclei, where rearrangements take place, and RNAi-mediated silencing of PGM abolishes DNA cleavage. This is the first in vivo evidence suggesting an essential endonucleolytic function of a domesticated piggyBac transposase.